Study of Revlimid With Doxil and Avastin for Patients With Platinum Resistant Ovarian Cancer

Condition(s) targeted: Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma

Intervention: Lenalidomide, Liposomal Doxorubicin, Bevacizumab (Drug); Revlimid, Doxil, Avastin (Drug)

Phase: Phase 1

Status: Terminated

Sponsored by: New Mexico Cancer Care Alliance

Official(s) and/or principal investigator(s):
Teresa Rutledge, MD, Principal Investigator, Affiliation: University of New Mexico

This study will test the feasibility of combining 3 drugs, Revlimid with Doxil and Bevacizumab,and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.

Official title: Phase IB Study of Lenalidomide (Revlimid®) With Liposomal Doxorubicin (Doxil®) and Bevacizumab (Avastin®) for Patients With Platinum Resistant Ovarian Cancer.

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum Tolerated Dose (MTD) of the 3 drug combination and recommend a dose for phase II studies.

Secondary outcome:

Progression-free survival (PFS) after treatment with Revlimid plus Avastin and Doxil.

Acute and subacute toxicities of Lenalidomide plus Doxil and Avastin for the treatment of ovarian cancer.

Detailed description: The combination of Doxil with Avastin has several aspects of interest to ovarian cancer treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is possible tumoral interstitial pressure via increased half-life (if liposomal egress is diminished) and decreased [42], 3) improved Doxil distribution, and 4) likely favorable toxicity profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar erythrodysesthesia or PPE). Lenalidomide has also antiangiogenic properties, with a different mechanism of action than Avastin. Given the preliminary results of the effect of the combination of Doxil with Avastin, showing an increase in progression-free survival, we are interested in using a new thalidomide analog to maximize the angiogenic inhibition. This study will test the feasibility of combining all 3 drugs, and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- EOC patients must be platinum resistant/refractory (see 1. 1 for definition) and be

considered by the attending physician capable of being treated in this study according to GCP.

- Measurable disease by RECIST criteria or evaluable disease by GCIC criteria

- No prior anthracycline or lenalidomide use, unless the dose received was equal or

less than one cycle and the patient did not progress on treatment.

- Subjects must have calculated creatinine clearance > 60ml/min by Cockcroft-Gault

formula during the escalation phase.

- Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault

formula during the expansion phase. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance > 30ml/min and < 60ml/min.

- Understand and voluntarily sign an informed consent form.

- All study participants must be registered into the mandatory RevAssist® program, and

be willing and able to comply with the requirements of RevAssist®.

- Females of childbearing potential (FCBP)† must have a negative serum or urine

pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to

and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.

- No contraindication to anticoagulation

Exclusion Criteria:

- Pregnant or breast feeding females. (Lactating females must agree not to breast feed

while taking lenalidomide).

- Concurrent use of other anti-cancer agents or treatments.

- Known seropositive for or active viral infection with human immunodeficiency virus

(HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.

- History of thromboembolic event within the last 3 months

- Known hypersensitivity to any component of Avastin

University of New Mexico Cancer Center, Albuquerque, New Mexico 87106, United States

Starting date: September 2010
Last updated: January 7, 2014